Exploiting medical-expert knowledge via a novel memetic algorithm for the inference of gene regulatory networks.

This study introduces an innovative memetic algorithm for optimizing the consensus of well-adapted techniques for the inference of gene regulation networks. Building on the methodology of a previous proposal (GENECI), this research adds a local search phase that incorporates prior knowledge about gene interactions, thereby enhancing the optimization process under the influence of domain expert. The algorithm focuses on the evaluation of candidate solutions through a detailed evolutionary process, where known gene interactions guide the evolution of such solutions (individuals). This approach was subjected to rigorous testing using benchmarks from editions 3 and 4 of the DREAM challenges and the yeast network of IRMA, demonstrating a significant improvement in accuracy compared to previous related approaches. The results highlight the effectiveness of the algorithm, even when only 5% of the known interactions are used as a reference. This advancement represents a significant step in the inference of gene regulation networks, providing a more precise and adaptable tool for genomic research.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

An Introductory Guide to Aligning Networks Using SANA, the Simulated Annealing Network Aligner.

Sequence alignment has had an enormous impact on our understanding of biology, evolution, and disease. The alignment of biological networks holds similar promise. Biological networks generally model interactions between biomolecules such as proteins, genes, metabolites, or mRNAs. There is strong evidence that the network topology-the "structure" of the network-is correlated with the functions performed, so that network topology can be used to help predict or understand function. However, unlike sequence comparison and alignment-which is an essentially solved problem-network comparison and alignment is an NP-complete problem for which heuristic algorithms must be used.Here we introduce SANA, the Simulated Annealing Network Aligner. SANA is one of many algorithms proposed for the arena of biological network alignment. In the context of global network alignment, SANA stands out for its speed, memory efficiency, ease-of-use, and flexibility in the arena of producing alignments between two or more networks. SANA produces better alignments in minutes on a laptop than most other algorithms can produce in hours or days of CPU time on large server-class machines. We walk the user through how to use SANA for several types of biomolecular networks

Unified Alignment of Protein-Protein Interaction Networks

Paralleling the increasing availability of protein-protein interaction (PPI) network data, several network alignment methods have been proposed. Network alignments have been used to uncover functionally conserved network parts and to transfer annotations. However, due to the computational intractability of the network alignment problem, aligners are heuristics providing divergent solutions and no consensus exists on a gold standard, or which scoring scheme should be used to evaluate them. We comprehensively evaluate the alignment scoring schemes and global network aligners on large scale PPI data and observe that three methods, HUBALIGN, L-GRAAL and NATALIE, regularly produce the most topologically and biologically coherent alignments. We study the collective behaviour of network aligners and observe that PPI networks are almost entirely aligned with a handful of aligners that we unify into a new tool, Ulign. Ulign enables complete alignment of two networks, which traditional global and local aligners fail to do. Also, multiple mappings of Ulign define biologically relevant soft clusterings of proteins in PPI networks, which may be used for refining the transfer of annotations across networks. Hence, PPI networks are already well investigated by current aligners, so to gain additional biological insights, a paradigm shift is needed. We propose such a shift come from aligning all available data types collectively rather than any particular data type in isolation from others

SANA NetGO: A combinatorial approach to using Gene Ontology (GO) terms to score network alignments

Gene Ontology (GO) terms are frequently used to score alignments between protein-protein interaction (PPI) networks. Methods exist to measure the GO similarity between two proteins in isolation, but pairs of proteins in a network alignment are not isolated: each pairing is implicitly dependent upon every other pairing via the alignment itself. Current methods fail to take into account the frequency of GO terms across the networks, and attempt to account for common GO terms in an ad hoc fashion by imposing arbitrary rules on when to "allow" GO terms based on their location in the GO hierarchy, rather than using readily available frequency information in the PPI networks themselves. Here we develop a new measure, NetGO, that naturally weighs infrequent, informative GO terms more heavily than frequent, less informative GO terms, without requiring arbitrary cutoffs. In particular, NetGO down-weights the score of frequent GO terms according to their frequency in the networks being aligned. This is a global measure applicable only to alignments, independent of pairwise GO measures, in the same sense that the edge-based EC or S3 scores are global measures of topological similarity independent of pairwise topological similarities. We demonstrate the superiority of NetGO by creating alignments of predetermined quality based on homologous pairs of nodes and show that NetGO correlates with alignment quality much better than any existing GO-based alignment measures. We also demonstrate that NetGO provides a measure of taxonomic similarity between species, consistent with existing taxonomic measures--a feature not shared with existing GO-based network alignment measures. Finally, we re-score alignments produced by almost a dozen aligners from a previous study and show that NetGO does a better job than existing measures at separating good alignments from bad ones

Soft Computing Techiniques for the Protein Folding Problem on High Performance Computing Architectures

The protein-folding problem has been extensively studied during the last fifty years. The understanding of the dynamics of global shape of a protein and the influence on its biological function can help us to discover new and more effective drugs to deal with diseases of pharmacological relevance. Different computational approaches have been developed by different researchers in order to foresee the threedimensional arrangement of atoms of proteins from their sequences. However, the computational complexity of this problem makes mandatory the search for new models, novel algorithmic strategies and hardware platforms that provide solutions in a reasonable time frame. We present in this revision work the past and last tendencies regarding protein folding simulations from both perspectives; hardware and software. Of particular interest to us are both the use of inexact solutions to this computationally hard problem as well as which hardware platforms have been used for running this kind of Soft Computing techniques.This work is jointly supported by the FundaciónSéneca (Agencia Regional de Ciencia y Tecnología, Región de Murcia) under grants 15290/PI/2010 and 18946/JLI/13, by the Spanish MEC and European Commission FEDER under grant with reference TEC2012-37945-C02-02 and TIN2012-31345, by the Nils Coordinated Mobility under grant 012-ABEL-CM-2014A, in part financed by the European Regional Development Fund (ERDF). We also thank NVIDIA for hardware donation within UCAM GPU educational and research centers.Ingeniería, Industria y Construcció